ID MSL7_MYCMM Reviewed; 2104 AA.
AC B2HIL7;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 27-MAR-2024, entry version 97.
DE RecName: Full=Phenolphthiocerol synthesis polyketide synthase type I Pks15/1;
DE AltName: Full=Beta-ketoacyl-acyl-carrier-protein synthase I;
DE EC=2.3.1.41;
GN Name=pks15/1; Synonyms=msl7; OrderedLocusNames=MMAR_1762;
OS Mycobacterium marinum (strain ATCC BAA-535 / M).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium ulcerans group.
OX NCBI_TaxID=216594;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-535 / M;
RX PubMed=18403782; DOI=10.1101/gr.075069.107;
RA Stinear T.P., Seemann T., Harrison P.F., Jenkin G.A., Davies J.K.,
RA Johnson P.D., Abdellah Z., Arrowsmith C., Chillingworth T., Churcher C.,
RA Clarke K., Cronin A., Davis P., Goodhead I., Holroyd N., Jagels K.,
RA Lord A., Moule S., Mungall K., Norbertczak H., Quail M.A.,
RA Rabbinowitsch E., Walker D., White B., Whitehead S., Small P.L., Brosch R.,
RA Ramakrishnan L., Fischbach M.A., Parkhill J., Cole S.T.;
RT "Insights from the complete genome sequence of Mycobacterium marinum on the
RT evolution of Mycobacterium tuberculosis.";
RL Genome Res. 18:729-741(2008).
RN [2]
RP FUNCTION AS A POLYKETIDE SYNTHASE, AND MUTAGENESIS OF CYS-211 AND SER-2039.
RC STRAIN=ATCC BAA-535 / M;
RX PubMed=19799378; DOI=10.1021/ja904792q;
RA He W., Soll C.E., Chavadi S.S., Zhang G., Warren J.D., Quadri L.E.;
RT "Cooperation between a coenzyme A-independent stand-alone initiation module
RT and an iterative type I polyketide synthase during synthesis of
RT mycobacterial phenolic glycolipids.";
RL J. Am. Chem. Soc. 131:16744-16750(2009).
CC -!- FUNCTION: Catalyzes the elongation by iterative transfer of p-
CC hydroxybenzoyl group from FadD22 (pHBA-S-FAdD22) to form p-
CC hydroxyphenylalkanoate (pHPA) intermediates during phenolphthiocerol
CC (PPOL) biosynthesis. PPOL is an important intermediate in the
CC biosynthesis of phenolic glycolipid (mycosid B).
CC {ECO:0000269|PubMed:19799378}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-[ACP] + H(+) + malonyl-[ACP] = a 3-oxoacyl-[ACP]
CC + CO2 + holo-[ACP]; Xref=Rhea:RHEA:22836, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9916, Rhea:RHEA-COMP:14125,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78776, ChEBI:CHEBI:138651;
CC EC=2.3.1.41; Evidence={ECO:0000255|PROSITE-ProRule:PRU10022};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP
CC synthases family. {ECO:0000305}.
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DR EMBL; CP000854; ACC40211.1; -; Genomic_DNA.
DR RefSeq; WP_012393570.1; NC_010612.1.
DR AlphaFoldDB; B2HIL7; -.
DR SMR; B2HIL7; -.
DR STRING; 216594.MMAR_1762; -.
DR KEGG; mmi:MMAR_1762; -.
DR eggNOG; COG0604; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR HOGENOM; CLU_000022_35_5_11; -.
DR OrthoDB; 4516163at2; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001190; Chromosome.
DR GO; GO:0034081; C:polyketide synthase complex; IDA:UniProtKB.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008610; P:lipid biosynthetic process; IDA:UniProtKB.
DR CDD; cd05195; enoyl_red; 1.
DR CDD; cd08956; KR_3_FAS_SDR_x; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 6.10.40.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 3.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH-like_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR036299; Polyketide_synth_docking_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF51; PHENOLPHTHIOCEROL_PHTHIOCEROL POLYKETIDE SYNTHASE SUBUNIT E; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF13602; ADH_zinc_N_2; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF21089; PKS_DH_N; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SMART; SM01294; PKS_PP_betabranch; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF101173; Docking domain B of the erythromycin polyketide synthase (DEBS); 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 3.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..2104
FT /note="Phenolphthiocerol synthesis polyketide synthase type
FT I Pks15/1"
FT /id="PRO_0000406361"
FT DOMAIN 41..464
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 935..1207
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2004..2079
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 571..887
FT /note="Acyltransferase"
FT /evidence="ECO:0000250"
FT REGION 935..1095
FT /note="Dehydratase"
FT /evidence="ECO:0000250"
FT REGION 935..1057
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1069..1207
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1400..1705
FT /note="Enoylreductase"
FT /evidence="ECO:0000250"
FT REGION 1718..1899
FT /note="Beta-ketoacyl reductase (KR)"
FT REGION 2081..2104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 211
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 346
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 386
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 662
FT /note="For acyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 967
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1128
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT BINDING 1530..1547
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1719..1734
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 2039
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 211
FT /note="C->A: The pHBA starter unit is not loaded onto
FT Pks15/1 and thus the pHPA intermediate is not produced."
FT /evidence="ECO:0000269|PubMed:19799378"
FT MUTAGEN 2039
FT /note="S->A: The pHBA starter unit is loaded onto Pks15/1,
FT but the pHPA intermediate is not produced."
FT /evidence="ECO:0000269|PubMed:19799378"
SQ SEQUENCE 2104 AA; 217744 MW; 7A33F823206BDCA5 CRC64;
MTTSGESADQ QNDKLFRYLK KVAVELDEAR ARLREYEQRA TEPVAVVGIG CRFPGGADGP
EGLWDLVSQG RDAVTEFPND RGWDTEGLFD PDPDAEGKTY TRWGAFVENA TNFDAGFFGI
PPSEVLAMDP QQRLMLEVSW EALEHAGIDP MSLRGSSTGV FTGIFAPSYG GKDVGALQGY
GLTGSPVSVA SGRVAYVLGL EGPALSVDTA CSSSLVAIHW AMASLRSGEC DMALAGGVTV
MGLPSIFVGF SRQRGLAADG RCKAFAAAAD GTGWGEGAGV LVLERLSDAQ RNGHNVLAVV
RGSAINQDGA SNGLTAPNGL AQQRVIQAAL ANCGLTSADV DVVEAHGTAT TLGDPIEAEA
LLATYGQGRP TDQPLWVGSI KSNMGHTQAA AGVAGVIKMV QAMRHGLMPA SLHVDEPSKR
VDWESGAVSV LAEARDWPDA GRPRRAGVSS FGISGTNAHV ILEEAPAPEA VPDSESNKGE
PSLPVVPWVI SARSAEALTA QAGRLLAHVQ ADPQSNPVDI GFSLAGRSAF EHRAVVVGAD
RQQLLTGLAT LADGAPGAGV VTGQAGSVGK TAVVFPGQGS QRIGMARELH DQLPVFAEAF
DAVADELDRH LRIPLREVMW GSDAALLDST EFAQPALFAV EVALFAALQR WGLQPDFVMG
HSVGELSAAY VAGVLTLADA AMLVVARGRL MQALPAGGAM VAVAAAEDEV LPSLTDGVGI
AAINAPKSVV ISGAEAAVTA ISDQFAQQGR RVHRLAVSHA FHSPLMEPML EEFARIAAQV
EAREPQIALV SNVTGELASA DGGFGSAQYW VEHVRRAVRF ADSARQLHTL GVTHFVEVGP
GSGLTGSIEQ SLAPAEAVVV SMLGKDRPEV ASVLTAFGQL FSTGMSVDWP AVFAGSGATR
VDLPTYAFQR RRFWEVPGAD GPADATGLGL GGAEHALLGA VVERPDSGGV VLTGRLALAD
QPWLADHVIG GVVLFPGAGF VELAIRAGDE VGCAVVEELV LAAPLVLHPG MGVQVQVIVG
AADDSGNRAL SVYSRGDQSE DWLLNAEGML GVEAASSGAD LSVWPPEGAE SVDISDGYAQ
LADRGYAYGP GFQGLVGVWR RDSELFAEVV APSGVAVDKM GMHPVVLDAV LHALGLTAEQ
NPDSDETKLP FCWRGVSLHA GGAGRVRARL TMSGPDSISV EIADAAGLPV LTVGALVTRA
MSAAQLRAAV AAAGGGAPDQ GPLDVIWSPI PLSGSGTNGS AQPAVVSWAD FCAGGDGGAA
GDAGVVVWEP NPAGEDVVGS VYAATHAALE VLQSWFDGDR AGTLVVLTHG AVAMPGENVS
DLAGAAVWGI VRSAQAENPG RIVLVDADAA VEAAELVAVG EPQLVVRSGA AHAARLAPAA
PLLAVPADES AWRLAAGGGG TLEDLVIEPC PEVQAPLAAG QVRVAVRAVG VNFRDVVAAL
GMYPGEAPPL GAEGAGVVLE VGPQVSGVAV GDSVMGFLGG AGPLSVVDQQ LITRMPQGWS
FAQAAAVPVV FLTALFGLQD LAKIQPGESV LIHAGTGGVG MAAVQLARHW GVEIFVTASR
GKWDTLRAMG FDDDHIGDSR TLDFEEKFLA VTDGRGVDVV LDSLAGDFVD ASLRLLVRGG
RFLEMGKTDI RDADKIAANY PGVWYRAFDL SEAGPVRMQE MLAEVRELFD TAVLHRLPVT
TWDVRCAPAA FRFMSQARHI GKVVLTMPSA LADGLADATV LITGATGAVG AVLARHMLDA
YGVRHLVLAS RRGDRAEGAA ELAAELSEAG ANVQVVACDV ADRDAVEAML ARLSGEYPPV
RGVIHAAGVL DDAVISSLTP ERIDTVLRAK VDAAWNLHEA TLDLDLSMFV LCSSIAATVG
SPGQGNYSAA NSFLDGLAAH RQAAGLAGIS VAWGLWEQSG GMAAHLSSRD LARMSRSGLA
PMNPEQAVGL LDAVLAINHP LMVATLLDRP ALEARAQAGG LPPLFAGVVR RPRRRQIEDT
GDAAQSKSAL AERLNGLSAG ERQDALVGLV CLQAAAVLGR PSPEDIDPEA GFQDLGFDSL
TAVELRNRLK SATGLTLPPT VIFDHPTPTA IAEYVGRQIP DSQATQAEEE KLPESDGEMV
SVTA
//
